Genomes and Genes
Summary: Desmoplakins are cytoskeletal linker proteins that anchor INTERMEDIATE FILAMENTS to the PLASMA MEMBRANE at DESMOSOMES.
- Fressart V, Duthoit G, Donal E, Probst V, Deharo J, Chevalier P, et al. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace. 2010;12:861-8 pubmed publisher..We wanted to address the potential impact of genotyping...
- Choi H, Gross J, Pokutta S, Weis W. Interactions of plakoglobin and beta-catenin with desmosomal cadherins: basis of selective exclusion of alpha- and beta-catenin from desmosomes. J Biol Chem. 2009;284:31776-88 pubmed publisher..Using purified proteins, we show that desmosomal cadherins and alpha-catenin compete directly for binding to plakoglobin, consistent with the absence of alpha-catenin in desmosomes...
- Franke W, Borrmann C, Grund C, Pieperhoff S. The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol. 2006;85:69-82 pubmed
- Rieger Christ K, Ng L, Hanley R, Durrani O, Ma H, Yee A, et al. Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses cell migration and tumorigenic potential. Br J Cancer. 2005;92:2153-9 pubmed..These results show that plakoglobin acts as a tumour suppressor gene in bladder carcinoma cells and the silencing of plakoglobin gene expression in late-stage bladder cancer is a primary event in tumour progression. ..
- Canes D, Chiang G, Billmeyer B, Austin C, Kosakowski M, Rieger Christ K, et al. Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo. Int J Cancer. 2005;113:841-8 pubmed..The results suggest that TSA inhibits bladder carcinoma cell growth and may be a useful, relatively nontoxic agent for consideration in the treatment of late-stage bladder tumors. ..
- Hu P, Berkowitz P, O Keefe E, Rubenstein D. Keratinocyte adherens junctions initiate nuclear signaling by translocation of plakoglobin from the membrane to the nucleus. J Invest Dermatol. 2003;121:242-51 pubmed
- Choi H, Park Snyder S, Pascoe L, Green K, Weis W. Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure. Nat Struct Biol. 2002;9:612-20 pubmed..In contrast to the elongated structures formed by other kinds of repeat motifs, the plakin repeats form a globular structure with a unique fold. A conserved basic groove found on the domain may represent an IF-binding site. ..
- Carayol N, Campbell A, Vachier I, Mainprice B, Bousquet J, Godard P, et al. Modulation of cadherin and catenins expression by tumor necrosis factor-alpha and dexamethasone in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2002;26:341-7 pubmed..We demonstrated, using Western blot analysis and immunofluorescence, that proinflammatory cytokines could be responsible for structural damage to the epithelium and that this process was potentially reversed by steroids. ..
- Hatzfeld M, Haffner C, Schulze K, Vinzens U. The function of plakophilin 1 in desmosome assembly and actin filament organization. J Cell Biol. 2000;149:209-22 pubmed
- Hall C, Li S, Li H, Creason V, Wahl J. Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 mutations disrupt desmosome assembly and stability. Cell Commun Adhes. 2009;16:15-27 pubmed publisher..These studies expand our understanding of desmosome assembly and dynamics. ..
- Papagerakis S, Shabana A, Depondt J, Pibouin L, Blin Wakkach C, Berdal A. Altered plakoglobin expression at mRNA and protein levels correlates with clinical outcome in patients with oropharynx squamous carcinomas. Hum Pathol. 2004;35:75-85 pubmed..The study also shows evidence that the level of expression and intracellular localization of plakoglobin may be useful in predicting the course of disease in patients with oropharyngeal SCC. ..
- Lapouge K, Fontao L, Champliaud M, Jaunin F, Frias M, Favre B, et al. New insights into the molecular basis of desmoplakin- and desmin-related cardiomyopathies. J Cell Sci. 2006;119:4974-85 pubmed
- Gloushankova N, Wakatsuki T, Troyanovsky R, Elson E, Troyanovsky S. Continual assembly of desmosomes within stable intercellular contacts of epithelial A-431 cells. Cell Tissue Res. 2003;314:399-410 pubmed..Such a diverse range of dynamic activities of desmosomes apparently produces flexible but tight cell-cell adhesion required for different morphogenetic events in epithelial structures. ..
- Zhurinsky J, Shtutman M, Ben Ze ev A. Plakoglobin and beta-catenin: protein interactions, regulation and biological roles. J Cell Sci. 2000;113 ( Pt 18):3127-39 pubmed..The functional difference between catenins is reflected in their differential involvement in embryonic development and cancer progression. ..
- Yang Z, Bowles N, Scherer S, Taylor M, Kearney D, Ge S, et al. Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Res. 2006;99:646-55 pubmed..These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development. ..
- Garcia Gras E, Lombardi R, Giocondo M, Willerson J, Schneider M, Khoury D, et al. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest. 2006;116:2012-21 pubmed..These findings could provide for the opportunity to identify new diagnostic markers and therapeutic targets in patients with ARVC. ..
- Lahtinen A, Lehtonen E, Marjamaa A, Kaartinen M, Helio T, Porthan K, et al. Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm. 2011;8:1214-21 pubmed publisher..Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive myocardial disorder caused by mutations of desmosomal cell adhesion proteins. The prevalence of these variants in the general population is unknown...
- Whittock N, Wan H, Morley S, Garzon M, Kristal L, Hyde P, et al. Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome. J Invest Dermatol. 2002;118:232-8 pubmed
- Sen Chowdhry S, Syrris P, McKenna W. Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2007;50:1813-21 pubmed
- Uzumcu A, Norgett E, Dindar A, Uyguner O, Nisli K, Kayserili H, et al. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome. J Med Genet. 2006;43:e5 pubmed
- Hobbs R, Amargo E, Somasundaram A, Simpson C, Prakriya M, Denning M, et al. The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling. FASEB J. 2011;25:990-1001 pubmed publisher..Our findings indicate that SERCA2-deficiency is sufficient to impede desmosome assembly and weaken intercellular adhesive strength via a PKC?-dependent mechanism, implicating SERCA2 as a novel regulator of PKC? signaling. ..
- Getsios S, Amargo E, Dusek R, Ishii K, Sheu L, Godsel L, et al. Coordinated expression of desmoglein 1 and desmocollin 1 regulates intercellular adhesion. Differentiation. 2004;72:419-33 pubmed..Collectively, these observations demonstrate that Dsg1 promotes the formation of intercellular adhesion complexes and suggest that the relative level of Dsg and Dsc expressed at the cell surface regulates this adhesive process. ..
- Al Amoudi A, Castaño Diez D, Devos D, Russell R, Johnson G, Frangakis A. The three-dimensional molecular structure of the desmosomal plaque. Proc Natl Acad Sci U S A. 2011;108:6480-5 pubmed publisher..Plakophilins are added as a molecular reinforcement to fill the gap between the formed plaque complexes and the plasma membrane. ..
- Kaplan S, Gard J, Carvajal Huerta L, Ruiz Cabezas J, Thiene G, Saffitz J. Structural and molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol. 2004;13:26-32 pubmed..Altered protein-protein interactions at intercalated disks likely cause both contractile and electrical dysfunction in Carvajal syndrome. ..
- Fontao L, Favre B, Riou S, Geerts D, Jaunin F, Saurat J, et al. Interaction of the bullous pemphigoid antigen 1 (BP230) and desmoplakin with intermediate filaments is mediated by distinct sequences within their COOH terminus. Mol Biol Cell. 2003;14:1978-92 pubmed
- Kitajima Y. New insights into desmosome regulation and pemphigus blistering as a desmosome-remodeling disease. Kaohsiung J Med Sci. 2013;29:1-13 pubmed publisher..KIF-skeletal scaffold through several associate proteins, including plakoglobin, plakophillin, and desmoplakins. As such, the desmosomal contacts between adjacent cells generate an intercellular KIF scaffold throughout the ..
- den Haan A, Tan B, Zikusoka M, LladÃ³ L, Jain R, Daly A, et al. Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Cardiovasc Genet. 2009;2:428-35 pubmed publisher..Compared with those without a desmosome gene mutation, individuals with a desmosome gene mutation had earlier-onset ARVD/C and were more likely to have ventricular tachycardia. ..
- Bolling M, Jonkman M. Skin and heart: une liaison dangereuse. Exp Dermatol. 2009;18:658-68 pubmed publisher..Knowledge of these skin features and early recognition of such a syndrome may provide opportunities to halt or slow down cardiac disease progression, treat arrhythmias and even prevent sudden death. ..
- Sumigray K, Chen H, Lechler T. Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. J Cell Biol. 2011;194:631-42 pubmed publisher..This work reveals essential desmosome-associated components that control cortical microtubule organization and unexpected roles for centrosomal proteins in epidermal function...
- Papagerakis S, Shabana A, Pollock B, Papagerakis P, Depondt J, Berdal A. Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. Hum Pathol. 2009;40:1320-9 pubmed publisher..Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients. ..
- Winn R, Bremnes R, Bemis L, Franklin W, Miller Y, Cool C, et al. gamma-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth. Oncogene. 2002;21:7497-506 pubmed..This study shows that gamma-catenin can function as an inhibitor of beta-catenin/TCF-dependent gene transcription and highlights gamma-catenin as a potentially novel tumor suppressor protein in a subset of human NSCLC cancers. ..
- Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002;71:1200-6 pubmed..Therefore, different DSP mutations might produce different clinical phenotypes, with different modes of inheritance. ..
- Wan H, South A, Hart I. Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference. Exp Cell Res. 2007;313:2336-44 pubmed..This study indicates that Dp may participate in the regulation of keratinocyte cell proliferation by, in part at least, regulating cell cycle progression. ..
- Syed S, Trinnaman B, Martin S, Major S, Hutchinson J, Magee A. Molecular interactions between desmosomal cadherins. Biochem J. 2002;362:317-27 pubmed
- Shiina H, Breault J, Basset W, Enokida H, Urakami S, Li L, et al. Functional Loss of the gamma-catenin gene through epigenetic and genetic pathways in human prostate cancer. Cancer Res. 2005;65:2130-8 pubmed..The gamma-catenin mutation related to Bcl-2 overexpression has a significant effect on the pathogenesis of HRPC. This is the first report to characterize the epigenetic and genetic regulation of gamma-catenin in human prostate cancer. ..
- Miravet S, Piedra J, Miro F, Itarte E, Garcia de Herreros A, Duñach M. The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin. J Biol Chem. 2002;277:1884-91 pubmed..These results indicate that Tcf-4 contains two different sites for binding of beta-catenin and plakoglobin, and the interaction of the latter hinders the transcriptional activity of the complex. ..
- Jonkman M, Pasmooij A, Pasmans S, van den Berg M, Ter Horst H, Timmer A, et al. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa. Am J Hum Genet. 2005;77:653-60 pubmed..The new dramatic phenotype, which we named "lethal acantholytic epidermolysis bullosa," underscores the paramount role of DP in epidermal integrity. ..
- Huen A, Park J, Godsel L, Chen X, Bannon L, Amargo E, et al. Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength. J Cell Biol. 2002;159:1005-17 pubmed..These data provide direct in vitro evidence that IF-membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion. ..
- Kurzen H, Münzing I, Hartschuh W. Expression of desmosomal proteins in squamous cell carcinomas of the skin. J Cutan Pathol. 2003;30:621-30 pubmed..Desmosomal proteins are highly regulated in cutaneous SCC. Only desmoglein 2 expression correlates with risk of metastasis. Desmosomes may still be functional in metastasizing tumor cells. ..
- Cao Y, Chang H, Li L, Cheng R, Fan X. Alteration of adhesion molecule expression and cellular polarity in hepatocellular carcinoma. Histopathology. 2007;51:528-38 pubmed..The decreased expression of symplekin may be an early step in the transformation of hepatocytes, whereas alteration of the expression of adherens junctions and desmosomes may indicate more serious changes. ..
- Vasioukhin V, Bowers E, Bauer C, Degenstein L, Fuchs E. Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol. 2001;3:1076-85 pubmed..DP is therefore required for assembly of functional desmosomes, maintaining cytoskeletal architecture and reinforcing membrane attachments essential for stable intercellular adhesion. ..
- Huber A, Weis W. The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell. 2001;105:391-402 pubmed..APC contains sequences homologous to the phosphorylated region of cadherin, and is likely to bind similarly. ..
- Lechler T, Fuchs E. Desmoplakin: an unexpected regulator of microtubule organization in the epidermis. J Cell Biol. 2007;176:147-54 pubmed..Loss of DP prevents accumulation of cortical microtubules in vivo and in vitro. Our work uncovers a differentiation-specific rearrangement of the microtubule cytoskeleton in epidermis, and defines an essential role for DP in the process...
- Sen Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna W. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation. 2007;115:1710-20 pubmed..Recognition of disease variants with early and/or predominant LV involvement supports adoption of the broader term arrhythmogenic cardiomyopathy. ..
- Protonotarios N, Tsatsopoulou A, Anastasakis A, Sevdalis E, McKoy G, Stratos K, et al. Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. J Am Coll Cardiol. 2001;38:1477-84 pubmed..Affected subjects who were homozygous experienced progressive disease with adverse prognosis. A minority of subjects who were heterozygous showed minor ECG/echocardiographic changes, but clinically significant disease did not develop. ..
- Vasioukhin V, Bauer C, Degenstein L, Wise B, Fuchs E. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell. 2001;104:605-17 pubmed..Thus, remarkably, features of precancerous lesions often attributed to defects in cell cycle regulatory genes can be generated by compromising the function of alpha-catenin. ..
- Norgett E, Hatsell S, Carvajal Huerta L, Cabezas J, Common J, Purkis P, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000;9:2761-6 pubmed..This suggests that the tail domain of desmoplakin is not required for establishing tissue architecture during development. ..
- Aaltomaa S, Lipponen P, Kärjä V, Lundstedt S, Lappi J, Kosma V. The expression and prognostic value of alpha-, beta- and gamma-catenins in renal cell carcinoma. Anticancer Res. 2004;24:2407-13 pubmed..15, p=0.004), high T-category (RR=2.70, p=0.0001) and high WHO grade (RR=2.24, p=0.025). The results show that immunohistochemical analysis of beta-catenin expression may be used as an indicator of aggressiveness in renal cell carcinoma. ..
- Asimaki A, Tandri H, Huang H, Halushka M, Gautam S, Basso C, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med. 2009;360:1075-84 pubmed publisher..Routine immunohistochemical analysis of a conventional endomyocardial-biopsy sample appears to be a highly sensitive and specific diagnostic test for ARVC. ..
- Miravet S, Piedra J, Castaño J, Raurell I, Franci C, Duñach M, et al. Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription. Mol Cell Biol. 2003;23:7391-402 pubmed
- Kurokawa A, Nagata M, Kitamura N, Noman A, Ohnishi M, Ohyama T, et al. Diagnostic value of integrin alpha3, beta4, and beta5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma. Cancer. 2008;112:1272-81 pubmed publisher..The expression levels of ITGA3, ITGB4, and ITGB5 with functional normalization by desmosomal or cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC. ..